rs727502862

chr17-44399142-C-Gchr17-44399142-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001002909.4(GPATCH8):c.2935G>C(p.Ala979Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000055 in 1,455,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: GPATCH8 NM_001002909.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.94

Genes affected

GPATCH8 (HGNC:29066): (G-patch domain containing 8) The protein encoded by this gene contains an RNA-processing domain, a zinc finger domain, a lysine-rich region and a serine-rich region. A mutation in the serine-rich region of the protein is thought to be associated with hyperuricemia (PMID: 21594610). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4203552).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPATCH8	NM_001002909.4	c.2935G>C	p.Ala979Pro	missense_variant	8/8	ENST00000591680.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPATCH8	ENST00000591680.6	c.2935G>C	p.Ala979Pro	missense_variant	8/8	2	NM_001002909.4	P1
GPATCH8	ENST00000587228.5	c.*2821G>C		3_prime_UTR_variant, NMD_transcript_variant	9/9	1
GPATCH8	ENST00000335500.8	n.4251G>C		non_coding_transcript_exon_variant	7/7	2
GPATCH8	ENST00000635257.1	n.3034G>C		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000550 AC: 8 AN: 1455798 Hom.: 0 Cov.: 31 AF XY: 0.00000690 AC XY: 5 AN XY: 724668

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000202

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Nov 01, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	26
Dann	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.75	D;D
PrimateAI	Uncertain	0.61	T
Sift4G	Benign	0.29	T
Polyphen		0.98	D
Vest4		0.52
MutPred		0.20		Gain of glycosylation at A979 (P = 0.0264);
MVP		0.56
MPC		0.18
ClinPred		0.62	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs727502862; hg19: chr17-42476510;